External validation of Systematic COronary Risk Evaluation 2 - Older Persons (SCORE2-OP) in the EPIC-Norfolk prospective population study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): EPIC Norfolk was supported by the Medical Research Council UK (programme grants numbers MRC G0401527, MRC G0701863, MRC G1000143) and Cancer Research UK (programme grant number CRUK 8257). Introduction The Systematic COronary Risk Evaluation 2 – Older Persons (SCORE2-OP) algorithm is developed to assess 10-year risk of fatal and non-fatal cardiovascular disease (CVD) in apparently healthy individuals aged ≥70 years. We evaluated the performance of SCORE2-OP in the European Prospective Investigation of Cancer Norfolk (EPIC-Norfolk) prospective population cohort. Purpose To validate the SCORE2-OP model in men and women aged 70-80 years without prior myocardial infarction or stroke. Methods We included individuals aged 70-80 without prior myocardial infarction or stroke. We compared SCORE2-OP (low-risk algorithm) calculated 10-year risk with 10-year observed event rates in the EPIC-Norfolk cohort. SCORE2-OP was calculated using baseline EPIC-Norfolk data (1993-1997). Cardiovascular events were defined as a composite outcome of (i) death due to ischemic heart disease, cardiac failure, cerebrovascular disease or peripheral-artery disease, (ii) non-fatal myocardial infarction or (iii) non-fatal stroke. Observed rates were adjusted for competing fatal events. We evaluated discriminative power using C-statistic and calibration by plotting predicted versus observed event rates and calculating the observed/predicted ratios. Results SCORE2-OP was evaluated in 3,712 individuals (54% women) with a median (IQR) age of 73 (72-75) years. Ten-year SCORE2-OP was 10.3% (95% confidence interval (CI) 10.2-10.4) versus observed CVD of 16.8% (95% CI 15.6-18.0), yielding a ratio of 1.6 (95% CI 1.5-1.7). Observed events consisted of 9.4% (95% CI 8.4-10.3) fatal CVD events, 10.6% (95% CI 9.6-11.5) non-fatal myocardial infarctions, 10.5% (95% CI 9.5-11.5) non-fatal strokes, adjusted for 68.9% (95% CI 67.4-70.4) competing mortality events. C-statistic was 0.60 (95% CI 0.58-0.63), with a calibration plot demonstrating underestimation of risk across sex and risk groups.(Figure). Conclusion SCORE2-OP underestimates risk in individuals aged 70-80 years, and demonstrates suboptimal discriminative ability. However some underestimation of risk is to be expected given the EPIC-Norfolk baseline between 1993-1997, a low SCORE2-OP calculated risk should not be used as a standalone argument to withhold preventive efforts in older individuals.